Pancreatic pseudocyst associated with eating disorder.

We describe a patient with an eating disorder and hyperamylasemia originating from the salivary glands, who developed pancreatitis with a huge pancreatic pseudocyst. A 40-year-old woman was referred for the treatment of an eating disorder that had persisted for 9 years. She was admitted with abdominal pain, diarrhea, and nausea. She had bilateral parotid enlargement with marked elevation of total serum amylase level (3288 IU/l; normal range, 60-220) and an isolated increase of salivary isoamylase activity. After her symptoms resolved, oral intake of food was commenced. She subsequently complained of abdominal pain; this was associated with a slight elevation of serum pancreatic isoamylase and lipase levels, and a huge pancreatic pseudocyst was detected. Percutaneous drainage of the pseudocyst was successful. Endoscopic retrograde cholangiopancreatography demonstrated irregularity of the pancreatic duct. Based on these findings, the final diagnosis was parotid enlargement and acute exacerbation of chronic pancreatitis associated with a pancreatic pseudocyst in a patient with an eating disorder.

Establishment and characterization of a new hamster pancreatic cancer cell line: the biological activity and the binding characteristics of EGF or TGF-alpha.

CONCLUSIONS: This new animal cell line may be a useful model to study the effect of growth factors on malignant cell proliferation and differentiation in both in vivo and in vitro systems. METHODS: We established a new pancreatic cancer cell line from pancreatic cancer in the hamster (HPC) induced by N-nitrosobis(2-oxopropyl)amine (BOP) and characterized its morphological, pathological, and biological patterns. RESULTS: Cells grew rapidly, with a doubling time of 22.5 h. Chromosome number ranged from 33 to 144, and flow cytometric analysis showed two peaks of DNA distribution as a proliferative pattern. Ultrastructural analyses using transmission and scanning electron microscopy of HPC cells revealed desmosomes and loose interdigitation, with pseudopods and microvilli on the cell surface. The overexpression of epidermal growth factor (EGF) receptors on HPC cells was shown by immunohistochemistry. Binding characteristics and biological activity of EGF and type alpha transforming growth factor (TGF-alpha) were studied. TGF-alpha stimulated DNA synthesis in a dose-dependent manner, whereas EGF was without effect. Scatchard analysis of 125I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites, where that of 125I-TGF-alpha showed only a single order. Regarding the effect of pH on 125I-EGF or 125I-TGF-alpha dissociation, one-half maximal dissociation of 125I-EGF or 125I-TGF-alpha occurred at pH 6.0 or 6.5, respectively. Characteristics of the EGF receptor are similar to those of cultured human pancreatic cancer cells.

Single-strand conformation polymorphism analysis of the epidermal growth factor receptor at codon 497.

A variant human epidermal growth factor (EGF) receptor (HER) with a transition (G to A) at codon 497, resulting in a substitution of a lysine for an arginine, was recently demonstrated in several human pancreatic cancer cell lines. In the present study, we compared the frequency of expression of wild-type (HER497R) and variant (HER497K) EGF receptors in normal and malignant pancreatic tissue samples using single-strand conformation polymorphism analysis. Both receptors were expressed in normal (42%) and malignant (46%) tissues. Three samples (two normal and one cancer) expressed only HER497K. The cancer sample that was homozygous for HER497K exhibited strong EGF receptor immunoreactivity. The high frequency of HER497K expression suggests that it is due to a relatively common polymorphism in the HER coding region. Its presence in some of the cancer samples suggests that, like the wild-type receptor, HER497K also has a role in pancreatic cancer.

A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling.

Epidermal growth factor (EGF) and type alpha transforming growth factor (TGF-alpha) bind to a specific region in subdomain III of the extracellular portion of the EGF receptor (EGFR). Binding leads to receptor dimerization, auto-and transphosphorylation on intracellular tyrosine residues, and activation of signal transduction pathways. We compared the binding and biological actions of EGF and TGF-alpha in Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or a variant EGFR that has an arginine-to-lysine substitution in the extracellular domain at codon 497 (HER497K) within subdomain IV of EGFR. Both receptors exhibited two orders of binding sites with radioiodinated EGF (125I-EGF). Similar results were obtained with 125I-TGF-alpha in cells expressing HER497R. In contrast, only one order of low-affinity binding sites was seen with 125I-TGF-alpha in the case of HER497K. Although EGF and TGF-alpha enhanced tyrosine phosphorylation of both receptors, CHO cells expressing HER497K exhibited an attenuated growth response to EGF and TGF-alpha and a reduced induction of the protooncogenes FOS, JUN, and MYC. Moreover, high concentrations of TGF-alpha (5 nM) inhibited growth in these cells but not in cells expressing HER497R. These findings indicate that a region in subdomain IV of EGFR regulates signal transduction across the cell membrane and selectively modulates that binding characteristics of TGF-alpha.

Cloning of a variant epidermal growth factor receptor.

The sequences encoding the full-length epidermal growth factor receptor (EGFR) were cloned from a cDNA library prepared from T3M4 cells. A transition (G to A) was identified at codon 497 of EGFR cDNA, resulting in the substitution of a lysine for an arginine. The same substitution was identified by sequencing cDNA derived from 3 of 7 additional human pancreatic cancer cell lines, one endometrial cancer cell line, and one lung cancer cell line, but not in A431 cells. Variant EGFR was always co-expressed with wild-type EGFR. Both sequences were present in genomic DNA from two cell lines expressing the variant receptor and in DNA from normal (3 of 7 individuals) human lymphocytes. These findings indicate that there are two alleles in this region of the EGFR gene, and that expression of variant EGFR is a common occurrence in normal and cancerous cells.

Successful removal of massive intragastric gallstones by endoscopic electrohydraulic lithotripsy and mechanical lithotripsy.

We describe a case of massive gallstones discharged into the stomach through a cholecystoduodenal fistula and the successful removal of these stones by endoscopic electrohydraulic lithotripsy (EEHL) and endoscopic mechanical lithotripsy (EML) for the prevention of gallstone ileus. A 60-yr-old woman was admitted with epigastric pain and nausea. Upper gastrointestinal tract examination demonstrated backflow of contrast medium from the duodenal bulb into the gallbladder. Endoscopic examination revealed a large fistula on the anterior wall of the duodenal bulb, and two brown stones (about 3 cm in diameter) were found in the stomach. To prevent gallstone ileus, removal of these stones was attempted. They were broken into pieces by EEHL, then crushed into smaller pieces by EML and removed orally. Chemical analysis showed the composition of the gallstones to be at least 98% cholesterol. The patient was discharged one month after removal of the gallstones and has remained asymptomatic.

Experimental study on multidisciplinary treatment of pancreatic cancer.

We investigated the antitumor effects of intratumoral (IT) injection of mitomycin-C (MMC), 5-fluorouracil (5FU), adriamycin (ADR), cisplatin (CDDP), streptozotocin (STZ), and interleukin-2 (IL-2) on well-differentiated pancreatic ductal adenocarcinoma (WD PaCa), a solid tumor model in the Syrian golden hamster. The growth of established palpable WD PaCa was not suppressed by intraperitoneal (IP) injection of these anticancer agents, whereas IT injection of MMC (1.0 mg/kg or more), 5FU (12.5 mg/kg or more), and CDDP (2.5 mg/kg or more) caused significant and marked suppression. The growth of established palpable WD PaCa was transiently suppressed by 50 Gy of local irradiation. The antitumor effect of irradiation was not enhanced by it injection of MMC before irradiation, whereas it was significantly enhanced by it injection after irradiation. Intraperitoneal injection of IL-2 (5 or 10 micrograms/d, 18 d) slightly suppressed the growth of established palpable tumors, but it injection of IL-2 caused significant and marked suppression, eliminating the tumor in 10-20% of the animals. Findings in this animal model of pancreatic cancer suggest that it treatment of anticancer agents or IL-2 might become an effective therapy for advanced pancreatic cancer.

Synergistic antitumor effect of interleukin-2 and irradiation on pancreatic cancer in Syrian golden hamsters.

The cooperative effect of interleukin-2 (IL-2) and radiotherapy was studied in pancreatic ductal adenocarcinoma implanted subcutaneously (s.c.) into Syrian golden hamsters. No cooperative antitumor effect was observed in animals given intraperitoneal injections of IL-2 (5 micrograms/hamster) from the 8th day after irradiation. Tumor regrowth was slightly inhibited in animals treated from the 15th and 24th day after irradiation, but the inhibition was not significant. In contrast, when IL-2 was injected intratumorally from the 18th day after irradiation, tumor regrowth was significantly inhibited. It was concluded that the antitumor effect of irradiation was enhanced by IL-2, especially by intratumoral injection after the restoration of immunological competence.

Intratumoral treatment of pancreatic cancer with mitomycin-C adsorbed to activated carbon particles. A clinical trial on 15 cases.

Fifteen patients with carcinoma of the pancreas were treated with intratumoral injection of mitomycin-C adsorbed by activated carbon particles (MMC-CH) under ultrasound guidance. Following the treatment, in 6 out of 13 patients, the serum CA 19-9 declined to 10-75% of that before the treatment. The pain was alleviated in 8 out 13 patients, and in 5 out of 8 of these patients the serum CA 19-9 declined. In one case treated with MMC-CH before total pancreatectomy, charcoal deposits were found in the tumor and in 17 regional lymph nodes along with degeneration of cancer cells around the deposited charcoal. The results indicate that intratumoral injection of MMC-CH might be one of the methods for the treatment of advanced pancreatic cancer.